Skip to main content
PMC home page
British Journal of Clinical Pharmacology logoLink to British Journal of Clinical Pharmacology
. 1983;16(Suppl 2):285S–290S. doi: 10.1111/j.1365-2125.1983.tb02302.x

Pharmacokinetics of brotizolam in healthy subjects following intravenous and oral administration

Roeline Jochemsen, J G J Wesselman, J Hermans, C J van Boxtel, D D Breimer
PMCID: PMC1428208  PMID: 6661374

Abstract

1 Pharmacokinetics and bioavailability of brotizolam after i.v. and oral administration were studied in healthy young volunteers.

2 Kinetic parameters after i.v. administration were: volume of distribution 0.66 ± 0.19 1/kg, total plasma clearance 113 ± 28 ml/min, distribution half-life 11 ± 6 min, and elimination half-life 4.8 ± 1.4 h (mean values ± s.d.).

3 Kinetic parameters after oral administration were: absorption lag-time 8 ± 12 min, absorption half-life 10 ± 11 min, and elimination half-life 5.1 ± 1.2 h (mean values ± s.d.).

4 Bioavailability of brotizolam was 70 ± 22% when calculated by comparing oral and intravenous area-under-curve values, corrected for intra-individual half-life differences. An alternative calculation method, which is relatively independent of large clearance variations, provided a bioavailability of 70 ± 24% (range: 47-117%).

Keywords: brotizolam i.v. and oral administration, pharmacokinetics, elimination half-life, healthy volunteers

Full text

PDF
286S

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Amrein R., Cano J. P., Eckert M., Coassolo P. Pharmakokinetik von Midazolam nach intravenöser Verabreichung. Arzneimittelforschung. 1981;31(12A):2202–2205. [PubMed] [Google Scholar]
  2. Breimer D. D. Pharmacokinetics and metabolism of various benzodiazepines used as hypnotics. Br J Clin Pharmacol. 1979;8(1):7S–13S. doi: 10.1111/j.1365-2125.1979.tb00449.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Divoll M., Greenblatt D. J., Harmatz J. S., Shader R. I. Effect of age and gender on disposition of temazepam. J Pharm Sci. 1981 Oct;70(10):1104–1107. doi: 10.1002/jps.2600701004. [DOI] [PubMed] [Google Scholar]
  4. Giles H. G., Sellers E. M., Naranjo C. A., Frecker R. C., Greenblatt D. J. Disposition of intravenous diazepam in young men and women. Eur J Clin Pharmacol. 1981;20(3):207–213. doi: 10.1007/BF00544599. [DOI] [PubMed] [Google Scholar]
  5. Greenblatt D. J., Allen M. D., Harmatz J. S., Shader R. I. Diazepam disposition determinants. Clin Pharmacol Ther. 1980 Mar;27(3):301–312. doi: 10.1038/clpt.1980.40. [DOI] [PubMed] [Google Scholar]
  6. Greenblatt D. J., Locniskar A., Ochs H. R., Lauven P. M. Automated gas chromatography for studies of midazolam pharmacokinetics. Anesthesiology. 1981 Aug;55(2):176–179. doi: 10.1097/00000542-198108000-00014. [DOI] [PubMed] [Google Scholar]
  7. Greenblatt D. J., Shader R. I., Franke K., MacLaughlin D. S., Harmatz J. S., Allen M. D., Werner A., Woo E. Pharmacokinetics and bioavailability of intravenous, intramuscular, and oral lorazepam in humans. J Pharm Sci. 1979 Jan;68(1):57–63. doi: 10.1002/jps.2600680119. [DOI] [PubMed] [Google Scholar]
  8. Jochemsen R., Breimer D. D. Assay of triazolam in plasma by capillary gas chromatography. J Chromatogr. 1981 May 8;223(2):438–444. doi: 10.1016/s0378-4347(00)80119-x. [DOI] [PubMed] [Google Scholar]
  9. Jochemsen R., Hogendoorn J. J., Dingemanse J., Hermans J., Boeijinga J. K., Breimer D. D. Pharmacokinetics and bioavailability of intravenous, oral, and rectal nitrazepam in humans. J Pharmacokinet Biopharm. 1982 Jun;10(3):231–245. doi: 10.1007/BF01059259. [DOI] [PubMed] [Google Scholar]
  10. Jochemsen R., Wesselman J. G., van Boxtel C. J., Hermans J., Breimer D. D. Comparative pharmacokinetics of brotizolam and triazolam in healthy subjects. Br J Clin Pharmacol. 1983;16 (Suppl 2):291S–297S. doi: 10.1111/j.1365-2125.1983.tb02303.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Nicholson A. N., Stone B. M., Pascoe P. A. Studies on sleep and performance with a triazolo-1, 4-thienodiazepine (brotizolam). Br J Clin Pharmacol. 1980 Jul;10(1):75–81. doi: 10.1111/j.1365-2125.1980.tb00504.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Pakes G. E., Brogden R. N., Heel R. C., Speight T. M., Avery G. S. Triazolam: a review of its pharmacological properties and therapeutic efficacy in patients with insomnia. Drugs. 1981 Aug;22(2):81–110. doi: 10.2165/00003495-198122020-00001. [DOI] [PubMed] [Google Scholar]
  13. Saletu B., Grünberger J., Volavka J., Berner P. Classification and bioavailability studies with WE 941 by quantitative pharmaco-EEG and clinical analyses. Arzneimittelforschung. 1979;29(4):700–704. [PubMed] [Google Scholar]

Articles from British Journal of Clinical Pharmacology are provided here courtesy of British Pharmacological Society

RESOURCES